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In addition to completing the Watson-Crick nucleobase matching "concept" (big pairs with small,
hydrogen bond donors pair with hydrogen bond acceptors),
artificially expanded genetic information systems
(AEGIS) also challenge DNA polymerases with a
complete set of mismatches, including wobble mismatches.
Here, we explore wobble mismatches with AEGIS with
DNA polymerase 1 from Escherichia coli. Remarkably, we
find that the polymerase tolerates an AEGIS:standard
wobble that has the same geometry as the G:T wobble that
polymerases have evolved to exclude but excludes a wobble
geometry that polymerases have never encountered in
natural history. These results suggest certain limits to "structural analogy" and "evolutionary guidance" as tools
to help synthetic biologists expand DNA alphabets.

Axiomatically, the density of information
stored in DNA, with just four nucleotides (GACT), is
higher than in a binary code, but less than it might be if
synthetic biologists succeed in adding independently
replicating nucleotides to genetic systems. Such addition
could also add additional functional groups, not found in
natural DNA but useful for molecular performance. Here,
we consider two new nucleotides (Z and P, 6-amino-5-
nitro-3-(1'-B-D-2'-deoxyribo-furanosyl)-2(1H)-pyridone
and 2-amino-8-(1'-B-D-2'-deoxyribofuranosyl)-imidazo-
[1,2-a]-1,3,5-triazin-4(8H)-one). These are designed to
pair via strict Watson?Crick geometry. These were added
to a laboratory in vitro evolution (LIVE) experiment; the
GACTZP library was challenged to deliver molecules that
bind selectively to liver cancer cells, but not to
untransformed liver cells. Unlike in classical in vitro
selection systems, low levels of mutation allow this system
to evolve to create binding molecules not necessarily
present in the original library. Over a dozen binding
species were recovered. The best had Z and/or P in their
sequences. Several had multiple, nearby, and adjacent Zs
and Ps. Only the weaker binders contained no Z or P at all.
This suggests that this system explored much of the
sequence space available to this genetic system and that
GACTZP libraries are richer reservoirs of functionality
than standard libraries.

Motivation: Despite advances in high-throughput sequencing, marine
metagenomic samples remain largely opaque. A typical sample contains
billions of microbial organisms from thousands of genomes and
quadrillions of DNA base pairs. Its derived metagenomic dataset
underrepresents this complexity by orders of magnitude because of
the sparseness and shortness of sequencing reads. Read shortness
and sequencing errors pose a major challenge to accurate species
and functional annotation. This includes distinguishing known from
novel species. Often the majority of reads cannot be annotated and
thus cannot help our interpretation of the sample.
Results: Here, we demonstrate quantitatively how careful assembly of
marine metagenomic reads within, but also across, datasets can alleviate
this problem. For 10 simulated datasets, each with species complexity
modeled on a real counterpart, chimerism remained within the
same species for most contigs (97%). For 42 real pyrosequencing
('454') datasets, assembly increased the proportion of annotated
reads, and even more so when datasets were pooled, by on average
1.6% (max 6.6%) for species, 9.0% (max 28.7%) for Pfam protein
domains and 9.4% (max 22.9%) for PANTHER gene families. Our results
outline exciting prospects for data sharing in the metagenomics
community. While chimeric sequences should be avoided in other
areas of metagenomics (e.g. biodiversity analyses), conservative
pooled assembly is advantageous for annotation specificity and sensitivity.
Intriguingly, our experiment also found potentia

SMC proteins are essential components of three protein complexes
that are
important for chromosome structure and function. The cohesin complex holds
replicated sister chromatids together, whereas the condensin complex has an
essential role in mitotic chromosome architecture. Both are involved in
interphase
genome organisation. SMC-containing complexes are large (>650 kDa for
condensin) and contain long anti-parallel coiled-coils. They are thus
difficult
subjects for conventional crystallographic and electron cryomicroscopic
studies.
Here we have used amino acid-selective cross-linking and mass spectrometry
(CLMS) combined with structure prediction to develop a full-length
molecular draft
3D-structure of the SMC2/SMC4 dimeric backbone of chicken condensin. We
assembled homology-based molecular models of the globular heads and hinges
with
the lengthy coiled-coils modelled in fragments, using numerous
high-confidence
cross-links and accounting for potential irregularity. Our experiments
reveal that
isolated condensin complexes can exist with their coiled-coil segments
closely
apposed to one another along their lengths and define the relative spatial
alignment
of the two anti-parallel coils. The centres of the coiled-coils can also
approach one
another closely in situ in mitotic chromosomes. In addition to revealing
structural
information, our cross-linking data suggest that both H2A and H4 may have
roles in
condensin interactions with chromatin.

More than 20% of all protein domains are currently annotated as "domains of unknown function" (DUFs). About 2,700 DUFs are found in bacteria compared with just over 1,500 in eukaryotes. Over 800 DUFs are shared between bacteria and eukaryotes, and about 300 of these are also present in archaea. A total of 2,786 bacterial Pfam domains even occur in animals, including 320 DUFs. Evolutionary conservation suggests that many of these DUFs are important. Here we show that 355 essential proteins in 16 model bacterial species contain 238 DUFs, most of which represent single-domain proteins, clearly establishing the biological essentiality of DUFs. We suggest that experimental research should focus on conserved and essential DUFs (eDUFs) for functional analysis given their important function and wide taxonomic distribution, including bacterial pathogens.

Summary: The Malaria Genome Exploration Tool (MaGnET) is a software tool
enabling intuitive 'exploration-style' visualization of functional
genomics data relating to the malaria parasite, Plasmodium falciparum.
MaGnET provides innovative integrated graphic displays for different
datasets, including genomic location of genes, mRNA expression data,
protein–protein interactions and more. Any selection of genes to explore
made by the user is easily carried over between the different viewers for
different datasets, and can be changed interactively at any point (without
returning to a search).